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CYP3A4*1B and CYP3A5*3 SNPs significantly impact the response of Egyptian candidates to high-intensity statin therapy to atorvastatin

Maslub MG, Daud NAA, Radwan MA, Sha'aban A, Ibrahim AG

Eur J Med Res, 2024 Nov 10;29(1):539.
PMID: 39523378 DOI: 10.1186/s40001-024-02109-7

BACKGROUND: A single nucleotide polymorphism (SNP) is a variation in the DNA sequence that results from the alteration of a single nucleotide in the genome. Atorvastatin is used to treat hypercholesterolemia. It belongs to a class of drugs called statins, which lower elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Research findings on the associations between the response to atorvastatin and genetic polymorphisms in CYP3A4 and CYP3A5 are inconclusive. The effects of CYP3A4*1B (rs2740574 C/T) and CYP3A5*3 (rs776746 T/C) on atorvastatin therapy have not been previously studied among Egyptians.
OBJECTIVE: This research aimed to investigate the effects of the genetic polymorphisms CYP3A4*1B and CYP3A5*3 on atorvastatin treatment in Egyptians.
METHODS: In this prospective cohort study, 100 subjects were genotyped for these SNPs. All participants were screened for serum lipid profiles, liver enzymes, total bilirubin (TB), and creatine kinase (CK) before and after 40 mg postatorvastatin therapy. Atorvastatin plasma levels were assessed posttreatment; atorvastatin pharmacokinetics were evaluated in five carriers of the CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes.
RESULTS: The allele frequencies of the CYP3A4*1B and CYP3A5*3 SNPs were 86% and 83%, respectively. The CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes significantly improved the serum triglyceride (TG) level (P

Matched MeSH terms: Hypercholesterolemia/genetics
A novel pathogenic variant of the LDLR gene in the Asian population and its clinical correlation with familial hypercholesterolemia

Chahil JK, Lye SH, Bagali PG, Alex L

Mol Biol Rep, 2012 Jul;39(7):7831-8.
PMID: 22544571 DOI: 10.1007/s11033-012-1626-8

Familial hypercholesterolemia (FH) is a disease implicated with defects in either, Low density lipoprotein receptor gene (LDLR), Apolipoprotein B-100 gene (APOB), the Proprotein convertase subtilisin/kexin type 9 gene (PCSK9) or other related genes of the lipid metabolism pathway. The general characterization of heterozygous FH is by elevated low-density lipoprotein (LDL) cholesterol and early-onset cardiovascular diseases, while the more severe type, the homozygous FH results in extreme elevated levels of LDL cholesterol and usually death of an affected individual by early twenties. We present here a novel non-synonymous, missense mutation in exon 14 of the LDLR gene in two siblings of the Malay ethnicity discovered during an in-house genetic test. We postulate that their elevated cholesterol is due to this novel mutation and they are positive for homozygous FH. This is the first report of a C711Y mutation in patients with elevated cholesterol in Asia.

Matched MeSH terms: Hypercholesterolemia/genetics*
Cholesterol lowering by Pediococcus acidilactici LAB4 and Lactobacillus plantarum LAB12 in adult zebrafish is associated with improved memory and involves an interplay between npc1l1 and abca1

Lim FT, Lim SM, Ramasamy K

Food Funct, 2017 Aug 01;8(8):2817-2828.
PMID: 28725889 DOI: 10.1039/c7fo00764g

This study assessed the cholesterol lowering effect of Pediococcus acidilactici LAB4 and Lactobacillus plantarum LAB12 using adult zebrafish. Animals were fed with a high cholesterol diet (HCD) with/without LAB for seven weeks. Serum and liver cholesterol was quantified using colorimetric and dye staining methods. Expressions of npc1l1 and abca1 in the liver and intestine and appa in the brain were quantified using RT-PCR. Serum and liver cholesterol was significantly lowered in LAB4- and LAB12-fed zebrafish (≤64% and ≤71%, respectively), with reduced liver cholesterol deposition. The cholesterol lowering effect was accompanied by down-regulation of npc1l1 in intestines (≤28.7%), up-regulation of abca1 in the liver (≥30.5%) and down-regulation of appa in the brain (≤24.5%). A moderately strong positive Pearson correlation (r = 0.617, p < 0.01) was found between appa and serum cholesterol. LAB-fed zebrafish exhibited improved spatial learning and memory. LAB4 and LAB12 can be potentially used in preventing hypercholesterolaemia and Alzheimer's diseases.

Matched MeSH terms: Hypercholesterolemia/genetics
Fulltext Association and interaction between dietary pattern and VEGF receptor-2 (VEGFR2) gene polymorphisms on blood lipids in Chinese Malaysian and Japanese adults

Yap RW, Shidoji Y, Hon WM, Masaki M

Asia Pac J Clin Nutr, 2012;21(2):302-11.
PMID: 22507619

Dietary pattern and genetic predisposition of each population have different impacts on lifestyle-related chronic diseases. This study was conducted to evaluate the association and interaction between dietary patterns and VEGFR2 or KDR gene polymorphisms on physical and biochemical risk factors of cardiovascular disease in two Asian populations (179 Chinese Malaysian and 136 Japanese adults).

Matched MeSH terms: Hypercholesterolemia/genetics*
Phaleria macrocarpa (Scheff.) Boerl fruit aqueous extract enhances LDL receptor and PCSK9 expression in vivo and in vitro

Chong SC, Dollah MA, Chong PP, Maha A

J Ethnopharmacol, 2011 Sep 1;137(1):817-27.
PMID: 21763412 DOI: 10.1016/j.jep.2011.06.041

Phaleria macrocarpa (Scheff.) Boerl (Pm) has been shown to reduce cholesterol level in vitro and in vivo experiment.

Matched MeSH terms: Hypercholesterolemia/genetics
Dietary supplementation of defatted kenaf (Hibiscus cannabinus L.) seed meal and its phenolics-saponins rich extract effectively attenuates diet-induced hypercholesterolemia in rats

Chan KW, Ismail M, Mohd Esa N, Imam MU, Ooi J, Khong NMH

Food Funct, 2018 Feb 21;9(2):925-936.
PMID: 29313544 DOI: 10.1039/c7fo01109a

Kenaf is one of the important commercial fiber crops worldwide and defatted kenaf seed meal (DKSM) is a secondary by-product from the kenaf industry. Thus, efforts to turn this low-cost agricultural waste into value-added functional food ingredients will definitely bring advantageous impacts to the community health, environment and economy. The present study was aimed to investigate the cardioprotective properties of DKSM and its phenolics-saponins rich extract (PSRE) in diet-induced hypercholesterolemic rat model. Hypercholesterolemia was induced in Sprague-Dawley rats via atherogenic diet feeding and dietary interventions were conducted by incorporating DKSM (15% and 30%) and equivalent levels of PSRE (2.3% and 4.6%, respectively, equivalent to the total content of phenolics and saponins in DKSM groups) into the atherogenic diets. After 10 weeks of DKSM and PSRE supplementation, the hepatosomatic index, hepatosteatosis, serum lipid profile, Castelli risk indexes as well as hepatic and renal functions of hypercholesterolemic rats were significantly improved (p < 0.05). Besides, the levels of hepatic Hmgcr and serum Pcsk9 were lowered, along with transcriptional upregulations of hepatic Cyp7a1, Abca1, Lcat, ApoA2 and ApoE (p < 0.05). The gene expression of hepatic Ldlr was marginally enhanced by DKSM supplementation (p > 0.05), but superiorly upregulated by PSRE (p < 0.05). The combined results showed that hypercholesterolemia and the atherogenic risk in rats were effectively attenuated by DKSM and PSRE supplementation, possibly via modulations of multiple vital processes in hepatic cholesterol metabolism. Furthermore, phenolics and saponins may be the bioactives conferring DKSM and PSRE with their anti-hypercholesterolemic properties. In conclusion, DKSM and PSRE are prospective cardioprotective functional food ingredients for hypercholesterolemic individuals.

Matched MeSH terms: Hypercholesterolemia/genetics*
Nigella sativa thymoquinone-rich fraction greatly improves plasma antioxidant capacity and expression of antioxidant genes in hypercholesterolemic rats

Ismail M, Al-Naqeep G, Chan KW

Free Radic Biol Med, 2010 Mar 01;48(5):664-72.
PMID: 20005291 DOI: 10.1016/j.freeradbiomed.2009.12.002

The antioxidant activities of the thymoquinone-rich fraction (TQRF) extracted from Nigella sativa and its bioactive compound, thymoquinone (TQ), in rats with induced hypercholesterolemia were investigated. Rats were fed a semipurified diet supplemented with 1% (w/w) cholesterol and were treated with TQRF and TQ at dosages ranging from 0.5 to 1.5 g/kg and 20 to 100 mg/kg body wt, respectively, for 8 weeks. The hydroxyl radical (OH(.))-scavenging activity of plasma samples collected from experimental rats was measured by electron spin resonance. The GenomeLab Genetic Analysis System was used to study the molecular mechanism that mediates the antioxidative properties of TQRF and TQ. Plasma total cholesterol and low-density-lipoprotein cholesterol levels were significantly decreased in the TQRF- and TQ-treated rats compared to untreated rats. Feeding rats a 1% cholesterol diet for 8 weeks resulted in a significant decrease in plasma antioxidant capacity, as measured by the capacity to scavenge hydroxyl radicals. However, rats treated with TQRF and TQ at various doses showed significant inhibitory activity toward the formation of OH(.) compared to untreated rats. Upon examination of liver RNA expression levels, treatment with TQRF and TQ caused the up-regulation of the superoxide dismutase 1 (SOD1), catalase, and glutathione peroxidase 2 (GPX) genes compared to untreated rats (P<0.05). In support of this, liver antioxidant enzyme levels, including SOD1 and GPX, were also apparently increased in the TQRF- and TQ-treated rats compared to untreated rats (P<0.05). In conclusion, TQRF and TQ effectively improved the plasma and liver antioxidant capacity and enhanced the expression of liver antioxidant genes of hypercholesterolemic rats.

Matched MeSH terms: Hypercholesterolemia/genetics